It is known that both the blood clotting process and the lysis of the blood clots are results of a proteolytic reaction. In the process of blood clotting the thrombin-fibrinogen reaction represents the key step wherein the fibrinogen, dissolved in the blood plasma, is converted into the insoluble fibrin polymer, whereas in the lypis process the fibrin polymer is cleaved into soluble fragments by the proteolytic action of plasmin. Good anticoagulants applicable in therapy are expected to inhibit the blood clotting process while permitting the plasmin-fibrin reaction (clot lysis) to proceed. Free tripeptide aldehyde salts of the structure D-phenylalanyl-L-prolyl-L-arginine-aldehyde (Hungarian patent specification No. 169,870 and Belgian patent specification No. 891,708) are anticoagulants possessing such properties. These compounds have no influence on the plasmin-fibrin reaction. In their presence, depending on their concentration, either no fibrin clot is formed or a loose one easily lysed by plasmin. However, it is also known that tripeptide-aldehydes, having a free amino terminal group, are rather unstable, rapidly losing their initial high enzyme inhibitory activity; only D-phenylalanyl-L-prolyl-L-arginine-aldehyde sulfate, described in Belgian patent specification No. 891,708, possesses significant stability, retaining its initial activity in cool solution (5.degree. C.) for a prolonged period.
On testing the stability of D-phenylalanyl-L-prolyl-L-arginine-aldehyde sulfate at higher temperatures it was found that in aqueous solution, at 80.degree. to 100.degree. C., it was transformed within hours, while at 37.degree. to 40.degree. C. within 10 to 14 days practically completely into a stable tricyclic compound, devoid of enzyme inhibitory activity. The structure of this compound [1,2,4,5,6,6a-hexahydro-1-benzyl-2-oxo-8-(4'-guanidino)-butyl-pyrrolo[1,2- a]imidazolo[2,1-c]pyrazine] was confirmed by mass spectrometry and NMR spectroscopy. Though it was found that the corresponding acyl-tripeptide-aldehydes fail to undergo similar conversion, nevertheless the acyl derivatives, e.g. t-butyloxycarbonyl-D-phenylalanyl-L-prolyl-L-arginine-aldehyde hemisulfate, inhibit both the thrombin-fibrinogen and the plasmin-fibrin reaction [Belgian patent specification No. 891,708 and S. Bajusz et al., in Peptides, Synthesis-Structure-Function (Eds.: H. D. Rich and E. Gross) Pierce Chem. Co., Rockford, Ill., USA, p. 817], they are less suitable for anticoagulant therapy.